Charles River Med Chem wiki highlighted article: May 2017
The Roles of Water in the Protein Matrix: A Largely Untapped Resource for Drug Discovery
This perspective explores water in the biological environment by adopting its point of view in such surroundings. The prevailing thermodynamic models of the past, where water was seen largely in terms of an entropic gain after its displacement by a ligand, are now known to be much too simplistic. The authors adopt a set of terminology that describes water molecules as being “hot” and “cold”, which they have defined as being easy and difficult to displace, respectively. The basis of these designations, which involve both enthalpic and entropic water contributions, are explored in several classes of biomolecules and structural motifs. The hallmarks for characterizing water molecules are examined, and computational tools for evaluating water-centric thermodynamics are reviewed. This perspective’s summary features guidelines for exploiting water molecules in drug discovery.